Staphylococcus-associated glomerulonephritis

Background

• A form of infection-associated glomerulonephritis caused by infection with Staphylococcus aureus or Staphylococcus epidermidis
• Occurs during acute infection (unlike post-streptococcal glomerulonephritis, which occurs following resolved infection)

Pathophysiology

• IgA-mediated immune complex deposition

Epidemiology

• Originally described with Staphylococcus epidermidis ventriculo-atrial shunt infections or endocarditis
• Now mostly caused by Staphylococcus aureus
• Most commonly occurs in older patients 40 to 60 years old, and people who inject drugs

Clinical Manifestations

• Glomerulonephritis that occurs during an acute staphylococcal infection
  • Syndrome characterized by AKI, microscopic hematuria, and nephrotic-range proteinuria
  • May be associated with any infection, including skin and soft tissue infection, abscess, osteomyelitis, endocarditis, intra-abdominal infection, and dental abscess
• Some patients have concurrent leukocytoclastic vasculitis similar to Henoch-Schönlein purpura
• Laboratory findings include occasional ANCA positivity (usually low titres), often low C3 with normal C4 (but both may be normal)

Complications and Prognosis

• Chronic kidney disease in 40 to 77%, with 43% progressing to end-stage renal disease

Diagnosis

Diagnostic Criteria

Definitive Diagnosis

• Culture-proven staphylococcal infection (ongoing or recent)
• Acute-onset proliferative glomerulonephritis with IgA- and complement C3-containing glomerular immune complex deposites, acute kidney injury, nephrotic-range proteinuria, and hematuria

Additional Criteria

• Presence of risk factors for infection: diabetes mellitus, intravenous drug use, recent surgical or invasive procedure, prosthetic devices such as pacemakers, heart valves or orthopaedic devices, poor dentition or tooth abscesses, multiple trauma with open wounds, non-healing ulcers or post-amputation wounds in diabetic patients, indwelling central or peripheral intravenous catheters or ventriculo-peritoneal shunt
• Low serum C3 levels
• Leukocytoclastic vasculitic rash (often has IgA staining on biopsy)
• Positive ANCA serology, though may be only mildly elevated
• Predominant C3 immunofluorescence with or without IgA staining in the mesangial and capillary walls with electron-dense immune deposits on ultrastructural examination
• Subepithelial humps seen with electron microscopy

Management

• Treat the underlying infection
• Supportive care for the symptoms of acute nephritis
  • Hypertension: calcium channel blockers preferred, but can also use ACEi or ARBs
  • Fluid overload: diuresis and salt restriction
  • May need dialysis
• Avoid immunosuppression

Further Reading

• Epidemiology, pathogenesis, treatment and outcomes of infection-associated glomerulonephritis. Nat Rev Nephrol. 2020;16(1):32-50. doi: 10.1038/s41581-019-0178-8